Background/Aims: The newborn screening (NBS) program in Oregon, USA, collects two routine specimens in all infants. The aim of our study was to determine the incidence of permanent versus transient congenital hypothyroidism (CH) in infants detected on the first versus second screening test. Methods: Thyroid function was determined in infants after the age of 3 years diagnosed with CH and born in Oregon between 2005 and 2011. Permanent hypothyroidism was defined as a TSH rise >10 mIU/ml after the first year on treatment or a TSH rise >6 mIU/ml with temporary discontinuation of l-thyroxine after the age of 3 years. Results: Of the cases detected on the first test, 72 of 87 (83%) were permanent and 15 of 87 (17%) were transient, while of the cases detected on the second test, 5 of 22 (23%) were permanent and 17 of 22 (77%) were transient (OR 16.3, p < 0.001). There was a female preponderance detected on the first screen versus a male preponderance on the second screen. Blood spot and serum thyroid function tests at diagnosis, before treatment, were not meaningfully different between the two groups. The mean l-thyroxine dose at the age of 3 years was greater on the first screen: 61.2 versus 36.6 μg/day. Conclusions: Infants detected on the second NBS specimen have a higher incidence of transient CH.

The Oregon Newborn Screening Laboratory converted GALT testing from a manual Beutler method to the automated PerkinElmer GSP GALT assay in February 2012. With this transition, the Laboratory has noted an increased number of specimens with abnormal screening results. Follow-up on these specimens has indicated a larger number of false positives for galactosemia, as well as the detection of G-6-PD not previously detected in the Beutler assay. These G-6-PD cases have been predominantly identified in infants noted as Asian/Pacific Islander from Hawaii, a participating state in the NW Regional NBS Program administered by the Oregon State Public Health Laboratory. Due to the increased number of specimens with abnormal screening results using the GSP GALT kit, and confirming as galactosemia false positives or G-6-PD, the Laboratory initiated a review of testing, follow-up, and diagnostic processes. This presentation covers the findings, decisions, and process changes made to accommodate the differences found in the GALT assay conversion.

We report the cases of 3 infants with congenital hypothyroidism detected with the use of our newborn screening program, with evidence supporting excess maternal iodine ingestion (12.5 mg/d) as the etiology. Levels of whole blood iodine extracted from their newborn screening specimens were 10 times above mean control levels. Excess iodine ingestion from nutritional supplements is often unrecognized. (J Pediatr 2012;161:760-2)

Objectives To use genotype analysis to determine the prevalence of the c.1436C -> T sequence variant in carnitine palmitoyltransferase 1A (CPT1A) among Alaskan infants, and evaluate the sensitivity of newborn screening by tandem mass spectrometry (MS/MS) to identify homozygous infants.Study design We compared MS/MS and DNA analyses of 2409 newborn blood spots collected over 3 consecutive months.Results Of 2409 infants, 166 (6.9%) were homozygous for the variant, all but one of whom were of Alaska Native race. None of the homozygous infants was identified by MS/MS on the first newborn screen using a C0/C16 + C18 cutoff of 130. Among 633 Alaska Native infants, 165 (26.1%) were homozygous and 218 (34.4%) were heterozygous for the variant. The prevalence was highest in Alaska's northern/western regions (51.2% of 255 infants homozygous; allele frequency, 0.7).Conclusions The CPT1A c.1436C -> T variant is prevalent among some Alaska Native peoples, but newborn screening using current MS/MS cutoffs is not an effective means to identify homozygous infants. The clinical consequences of the partial CPT1A deficiency associated with this variant are unknown. If effects are substantial, revision of newborn screening, including Alaska-specific MS/MS cutoffs and confirmatory genotyping, may be needed. (J Pediatr 2011; 158: 46-51).

OBJECTIVE To determine the type and incidence of hyperthyroxinemic disorders detected by follow-up of infants with elevated screening total T4 (TT4) values. STUDY DESIGN Infants born in Oregon with a screening TT4 measurement >3 SD above the mean were offered enrollment. Serum TT4, free T4, total T3, free T3, and thyroid-stimulating hormone concentrations were measured in study infants and their mothers. RESULTS Over a 20-month period, 101 infants (51 boys) and their mothers enrolled in the study (of 241 eligible infants), from a total screening population of 80,884; 17 infants were identified with persistent hyperthyroxinemia (TT4 >16 microg/dL). Ten had thyroxine-binding globulin excess (1:8088), 5 had evidence for increased T4 binding but not thyroxine-binding globulin excess (1:16,177), and 2 had findings compatible with thyroid hormone resistance (1:40,442); the other 84 infants had transient hyperthyroxinemia. Sequence analysis revealed a point mutation in the thyroid hormone receptor-beta gene in one infant with thyroid hormone resistance; no mutation was identified in the other infant. CONCLUSIONS Although neonatal Graves' disease occurs in approximately 1 in 25,000 newborn infants, we did not detect any case among 80,884 infants, most likely because their mothers were receiving antithyroid drugs. Although the other hyperthyroxinemic disorders in the aggregate occur frequently (1:4758) and may benefit from detection, in general they do not require treatment.

OBJECTIVES:To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism (CH) by evaluating the time course of rise of thyroxine (T(4)) and free T(4) concentrations into an established "target range" and normalization of thyroid-stimulating hormone (TSH) and to reevaluate the "target range" for T(4) and free T(4) concentrations during the first 2 weeks of CH treatment.STUDY DESIGN:Infants of birth weight 3 to 4 kg with CH (n = 47) detected by newborn screening were randomly assigned into three L-thyroxine treatment dose arms: 37.5 microg/day (group 1); 62.5 microg/day for 3 days, then 37.5 microg/day (group 2); and 50 microg/day (group 3). Serum T(4), free T(4), triiodothyronine (T(3)), free T(3), and TSH were measured before treatment and at 3 days and 1, 2, 4, 8, and 12 weeks after treatment.RESULTS:T(4) and free T(4) concentrations increased into the target range (10 to 16 microg/dL) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1; 50 microg/day (average 14.5 microg/kg/day) provided the most rapid normalization of TSH by 2 weeks. With the use of linear regression analysis of T(4) versus TSH or free T(4) versus TSH plots, the intercept at the lower range of normal for TSH (1.7 mU/L) showed T(4) = 19.5 microg/dL and free T(4) = 5.23 ng/dL.CONCLUSIONS:Initial dosing of 50 microg/day (12-17 microg/kg per day) raised serum T(4) and free T(4) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy. We recommend consideration of a somewhat higher "target range" of 10 to 18 microg/dL for T(4) and 2 to 5.0 ng/dL for free T(4) during the first 2 weeks of L-thyroxine treatment. After 2 weeks of treatment, the target range drops to 10 to 16 microg/dL for T(4) and 1.6 to 2.2 for free T(4).

Environmental contamination of drinking water has been observed for perchlorate, a chemical able to affect thyroid function. This study examines whether that exposure affected the thyroid function of newborns. Neonatal blood thyroxine (T4) levels for days 1 to 4 of life were compared for newborns from the city of Las Vegas, Nevada, which has perchlorate in its drinking water, and those from the city of Reno, Nevada, which does not (detection limit, 4 micrograms/L [ppb]). This study is based on blood T4 analyses from more than 23,000 newborns in these two cities during the period April 1998 through June 1999. No difference was found in the mean blood T4 levels of the newborns from these two cities. Drinking water perchlorate levels measured monthly for Las Vegas ranged during this study period from non-detectable for 8 months to levels of 9 to 15 ppb for 7 months. Temporal differences in mean T4 level were noted in both cities but were unrelated to the perchlorate exposure. This study was sufficiently sensitive to detect the effects of gender, birth weight, and the day of life on which the blood sample was taken on the neonatal T4 level, but it detected no effect from environmental exposures to perchlorate that ranged up to 15 micrograms/L (ppb).

BACKGROUND:The effect of perchlorate in drinking water on neonatal blood thyroid-stimulating hormone (thyrotropin; TSH) levels was examined for Las Vegas and Reno, Nevada.METHODS:The neonatal blood TSH levels in Las Vegas (with up to 15 microg/L (ppb) perchlorate in drinking water) and in Reno (with no perchlorate detected in the drinking water) from December 1998 to October 1999 were analyzed and compared. The study samples were from newborns in their first month of life (excluding the first day of life) with birth weights of 2, 500-4,500 g. A multivariate analysis of logarithmically transformed TSH levels was used to compare the mean TSH levels between Las Vegas and Reno newborns, with age and sex being controlled as potential confounders.RESULTS:This study of neonatal TSH levels in the first month of life found no effect from living in the areas with environmental perchlorate exposures of </=15 microg/L (P = 0.97).CONCLUSIONS:This study, which was sensitive enough to detect the effects of age and gender on neonatal blood TSH levels, detected no effect from environmental exposures to perchlorate.

Objectives: To determine the type and frequency of thyroid disorders detected in infants with low thyroxine (T4) and nonelevated thyroid-stimulating hormone (TSH) screening test results in the Northwest regional Newborn Screening Program (NWRNSP) over the 20-year period from Mag 1975 to Mag 1995 and to determine the effect of follow-up of these infants on the overall recall fate.Study design: The NWRNSP requests a serum specimen in infants with an absolute T4 level < 38.6 nmol/L <3 mg/dl) and in infants with two filter paper T4 concentrations less than the 3%, regardless of the TSH concentration. We conducted a retrospective analysis of infants who were followed up because of low T4 and nonelevated TSH concentrations on newborn screening. To determine the effect of follow-up of infants with lo Lv T4 levels, nonelevated TSH concentrations on the recall rate,we selected 1 ear (1994) far review Serum sample requests were evaluated to determine the reason for the request.Results: Over this 20-year period, the NWRNSP detected 450 infants with primary hypothyroidism among 1,747,805 infants screened (1:3,884). Of these, 416 were detected on the basis of low T4 levels and nonelevated TSH screening test results, whereas an additional 34 infants with primary hypothyroidism and 29 infants with hypopituitary hypothyroidism were detected as a result of followup of low T4 levels and nonelevated TSI-I screening test results. This included 25 infants with delayed TSH rise (1:67,226), 9 infants with mild hypothyroidism (TSH levels <25 mU/L) (1:194,212), 29 infants with hypopituitary hypothyroidism (1:60,269)1 and 434 infants with T4-binding globulin deficiency (1:4,027). Excluding those with T4-ginding globulin deficiency, the false-positive rate was 43.5:1. This compares with an overall false-positive rate of 12:1 for our screening program.Conclusion: Follow-up of infants with lo T4 and nonelevated TSH concentration on screening led to the detection of 63 additional infants with hypothyroidism, for an overall frequency of 1:27.743. We believe this yield justifies continued follow-up of infants with low T4 levels, nonelevated (TSH) screening rest results in our program.

Most newborn screening programs using a primary T4 screen, with TSH measurement in specimens below a T4 cutoff, choose not to follow-up infants with low T4 and “non-elevated” (typically <25) TSH concentrations. The Northwest Regional Screening Program (NWRSP), which obtains two routine filter paper (FP) specimens in infants born in Oregon and in most infants in Idaho, Alaska, and Nevada, requests a serum specimen in infants with two FP T4 concentrations <3% and in infants with absolute T4< 3ug/dl even when the FP TSH is “not elevated”. To determine the type and frequency of thyroid disorders detected in infants with low T4 and “non-elevated” TSH concentrations, we examined the results of the NWRSP from May 1975 to May 1995. Over this 20 year period, the NWRSP screened 1,747,805 infants. Follow-up of infants with low T4s and“non-elevated” TSHs on screening detected 25 infants with delayed TSH rise (1:67,226), 9 infants with mild hypothyroidism (TSH<25)(1:194,212), 26 infants with hypopituitary hypothyroidism (1:67,223), and 434 infants with TBG deficiency (1:4027). Mean thyroid values were as follows:Table In 1994, this approach led to a recall of 116 infants, including 29 with TBG deficiency and 2 with hypopituitary hypothyroidism. Excluding those with TBG deficiency, the false positive rate was 1:43.5. Newborns who were premature or ill were found with disproportionate frequency among infants with these laboratory values. Thus, the majority of these infants are normal or have TBG deficiency; therefore the psychological harm in creating the “vulnerable” child vs. identifying the rare child with delayed TSH rise, mild hypothyroidism, or hypopituitary hypothyroidism (overall detection rate 1:29, 130) must be evaluated. The NWRSP continues to follow-up infants with low T4 and“non-elevated” TSH levels.

We examined the results of the Northwest Regional Screening Program from May 1975 to June 1991 to determine the prevalence of inherited thyroxine-binding globulin (TBG) deficiency and its effect on thyroid hormone concentrations in infants. Serum thyroxine (T4), triiodothyronine resin uptake (T3RU), and thyrotropin values were requested of physicians caring for all infants with a single filter paper T4 level < 38.6 nmol/L (3 micrograms/dl) or a T4 level < 3rd percentile on two filter paper tests (at birth and 2 to 6 weeks of age). From 1,367,724 infants screened in five states, TBG deficiency, an X-linked disorder, was identified in 317 infants (285 boys). For the entire screening program the calculated frequency of TBG deficiency was 1:4315 infants (1:2400 for boys). In Oregon, where 95% of infants have two screening tests performed, the calculated frequency was somewhat higher (1:3080 infants; 1712 boys) and is probably more accurate. The mean serum T4 concentration for TBG-deficient boys was 41.9 nmol/L (3.26 micrograms/dl); 31% had values < 25.7 nmol/L (2.0 micrograms/dl). The mean serum T4 concentration for TBG-deficient girls was 60.2 nmol/L (4.68 micrograms/dl), with none < 2.0 micrograms/dl. The mean T3RU value was 0.472 in TBG-deficient boys, and 0.412 in TBG-deficient girls; the T3RU value was > 0.55 in 24% of TBG-deficient boys but was > 0.55 in only one girl. Free serum T4 levels were normal in all 56 TBG-deficient infants studied, and TBG levels were low in all 20 infants studied. Inherited TBG deficiency is common in boys in the Northwest, with a frequency of 1:1700 and a male/female ratio of 8.9:1. Boys with TBG deficiency have mild, moderate, or severe alterations in total T4 and T3RU values, but severe deficiency is rare in girls.